Our objective is a generalized understanding of the mechanisms by which oxygen supports life, in terms of the structures of oxidases, oxygen, and substrates, and of mechanisms of oxygen-activating reactions. We propose to investigate selected dioxygenase, and mixed function oxidase structure and function with oxidases containing copper or heme at their active sites. We propose to continue our biochemical and biophysical studies by (1) determining the structures of active sites and the related protein structures of copper and heme oxidases, (2) characterizing the reactions which take place between these oxidases, their substrate, and O2, (3) determining the fates of products when these are metastable and reactive, (4) seeking new techniques for forming, detecting, and characterizing functional enzyme complexes of oxygen and substrates. We propose to formulate our generalized understanding of oxidase structure and mechanism as a publication. We propose also to commence an exploration of the metabolic consequences of hypoxia on the functions of dioxygenases and mixed function oxidases. BIBLIOGRAPHIC REFERENCES: Mason, H.S., Binuclear Copper Clusters as Active Sites for Oxidases. Proceedings International Symposium on Fe and Cu Proteins, Honolulu 1975. Plenum Press, 1976, in press. McMahill, P., Blackburn, N., and Mason, H.S., An Interesting Reaction of Cupric Ions with Ferricyanide and Ferrocyanide, in Proceedings International Symposium on Fe and Cu Proteins, Honolulu 1975. Plenum Press, 1976, in press.